FDA Approves First Drug for Exelixis of South San Francisco
The Food and Drug Administration today approved the Exelixis (NASDAQ: EXEL) compound cabozantinib for the treatment of patients with progressive, metastatic thyroid cancer, giving the 18-year-old company its first marketable drug.
The FDA decision is an important watershed for the South San Francisco company. However, the marketing approval in medullary thyroid cancer opens no immediate gateway to substantial revenues for Exelixis, because the patient population with the orphan disease is very small.
But Exelixis hopes the FDA nod is the first step in the development of cabozantinib as a lucrative oncology franchise, because early-stage trials have suggested that the compound may deliver benefits in a range of different cancers.
“It’s the broad activity of cabozantinib that we think is very exciting,’’ said Exelixis CEO Michael Morrissey in an interview with Xconomy this month.
The next crucial test of cabozantinib’s promise is expected in 2014, when Exelixis anticipates data from two Phase III trials in advanced forms of prostate cancer, one of the top cancer types afflicting men. The American Cancer Society estimates that 241,740 men will be diagnosed with prostate cancer in the United States in 2012, and 28,170 will die of the disease.
Cabozantinib is a product of the in-house drug discovery and synthesis program at Exelixis, which formerly operated an industrialized, high-throughput screening center to identify promising drug candidates. The South San Francisco company has scaled back its discovery operations over the past two years to focus on cabozantinib. Exelixis holds sole ownership of the compound. Bristol-Myers Squibb ended a partnership in its development in 2010.
Cabozantinib is designed to prevent two processes that allow cancer to progress. The first is angiogenesis—the formation of blood vessels to nourish tumor growth. The second deadly process is metastasis—the spread of tumor cells to other parts of the body.
In June 2012, results from Exelixis’ Phase III EXAM trial in medullary thyroid cancer were presented at the annual ASCO (American Society of Clinical Oncology) meeting. The data indicated that the drug delays the worsening of the disease, though it may not extend the lifespan of patients.
Trial subjects given cabozantinib had a median progression-free survival of 11.2 months, compared with 4.0 months for those given a placebo.
The FDA granted Exelixis a priority review, setting Nov. 29 as the target date for a decision. After an FDA advisory panel told Exelixis in late August that it didn’t need to appear at a scheduled meeting to review pending drug applications, observers speculated that cabozantinib was headed for approval.
Though the agency has recently issued some approval decisions ahead of their announced decision dates, though, Exelixis had to wait out the deadline. The FDA-approved label for the drug, which will be sold under the brand name Cometriq, will come with boxed warnings about possible side effects: perforations and fistulas, and hemorrhage.
“The approval of Cometriq is an important milestone for patients with progressive, metastatic medullary thyroid cancer, their families, and their physicians, as well as for Exelixis,” said Morrissey in a company press release.
“We are grateful to the many patients who participated in the clinical development of Cometriq in MTC, and we are committed to making this important new therapy available as quickly as possible,” Morrissey said.
Exelixis said in a webcast today that cabozantinib will be priced at $9,900 per 28-day supply.
Exelixis also announced today that the European Medicines Agency has accepted the company’s application for review of cabozantinib as a treatment for late-stage medullary thyroid cancer.
The American Cancer Society estimates that 56,460 people will be diagnosed with thyroid cancer in the United States in 2012, and 1,780 people will die of the disease. Medullary thyroid cancer, or MTC, develops in a subset of thyroid gland cells, called C cells. The disease makes up about 4 percent of thyroid cancer cases, the cancer society estimates.
AstraZeneca, whose drug vandetanib (Caprelsa) was approved for medullary thyroid cancer in 2011, earned revenues of $19 million from the product during the first nine months of 2012, the company said in an earnings press release.
Exelixis estimates that the population of thyroid cancer patients who would benefit from the drug is 500 to 700 people in US, and about the same for Europe.
Exelixis faces higher hurdles in prostate cancer than it did in its thyroid cancer program. If cabozantinib were eventually approved as a prostate cancer treatment, it would enter an increasingly competitive field. New drugs for late-stage prostate cancer include enzalutamide (Xtandi), developed by Medivation of San Francisco and Astellas Pharma; Johnson & Johnson’s abiraterone (Zytiga); and the cancer vaccine sipuleucel-T (Provenge).
In Exelixis’s COMET-1 trial in late-stage prostate cancer, the company hopes to prove that subjects on cabozantinib have an improved overall survival—that is, they live longer. In the COMET-2 trial, Exelixis hopes to show that cabozantinib reduces pain in subjects whose prostate cancer has spread to their bones.
Morrissey says Exelixis has enough cash to fund its own operations, including the two prostate cancer trials, into 2014. He says the company may also start a trial in another cancer type, such as liver or kidney cancer, in 2013.
In August, Exelixis raised $416.1 million by selling 30 million shares and issuing convertible notes. The company ended the third quarter with $674.7 million in cash, marketable securities, and short-term and long-term investments. But the company also faces a series of debt repayments.
Morrissey says Exelixis would consider teaming up with a partner to develop cabozantinib.
“We would be open to the right deal at the right time at the right terms,’’ Morrissey said earlier this month. “Doing it by ourselves is the overall default decision.’’
In the meantime, Exelixis depends on occasional revenues from milestone payments that may flow from drug development partnerships with Sanofi, Bristol-Myers Squibb, and other companies.
Exelixis shares are trading lower than their 52-week high of $6.95, though the price rose modestly in the past two weeks to close at $5.28 on Nov. 28, the eve of the FDA decision date. In intraday trading after the FDA announcement, the shares were trading down slightly at $5.24.